Direct, Indirect, and Combined Extracranial-to-Intracranial Bypass for Adult Moyamoya Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults. METHODS: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales. RESULTS: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48-0.79]; P<0.0001; OR, 0.44 [0.32-0.59]; P<0.0001; OR, 0.56 [0.42-0.74]; P<0.0001; OR, 3.1 [2.5-3.8]; P=0.0001) and combined (OR, 0.53 [0.41-0.69]; P<0.0001; OR, 0.28 [0.2-0.41]; P<0.0001; OR, 0.41 [0.3-0.56]; P<0.0001; OR, 3.1 [2.8-4.3]; P=0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7-5.6]; P<0.0001) and direct (OR, 4.12 [2.34-7.25]; P<0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23-0.60]; P<0.001; OR, 0.49 [0.31-0.77]; P=0.002) and combined (OR, 0.23 [0.12-0.43]; P<0.00001; OR, 0.30 [0.18-0.49]; P<0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18-3.58]; P=0.01). CONCLUSIONS: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.

Extracranial-Intracranial Cerebral Revascularization for Atherosclerotic Vessel Occlusion: An Updated Systematic Review of the Literature.

BACKGROUND: Atherosclerotic steno-occlusive cerebrovascular disease includes extracranial carotid occlusive and intracranial atherosclerotic disease. Despite the negative findings in Carotid Occlusion Surgery Study (COSS), many large centers continue to report favorable results for revascularization surgery in select groups of patients. The aim of our study was to perform an updated systematic review to investigate the role of revascularization surgery for atherosclerotic steno-occlusive patients in the modern era. METHODS: Five independent reviewers performed Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided literature searches in October 2022 to identify articles reporting clinical outcomes in adult patients undergoing bypass for atherosclerotic steno-occlusive disease. Primary endpoints used were perioperative and long-term ischemic strokes, intracerebral hemorrhage, bypass patency, and favorable clinical outcomes. Study quality was evaluated with Newcastle-Ottawa, JADAD, and the Oxford Center for Evidence-Based Medicine scales. RESULTS: A total of 6709 articles were identified in the initial search. Of these articles, 50 met the inclusion criteria and were included in the systematic review. A notable increase in the proportion of articles published over the past 10 years was observed. There were 6046 total patients with 4447 bypasses performed over the period from 1978 to 2022. The average length of follow-up was 2.75 ± 2.71 years. The average Newcastle-Ottawa was 6.23 out of 9 stars. There was a significant difference in perioperative stroke (odds ratio [OR], 0.65 [0.48-0.87]; P = 0.004), long-term ischemia (OR, 0.32 [0.23-0.44]; P < 0.0001), overall ischemia (OR, 0.36 [0.28-0.44]; P < 0.0001), and favorable outcomes (OR, 3.63 [2.84-4.64]; P < 0.0001) when comparing pre-COSS to post-COSS time frames in favor of post-COSS. CONCLUSIONS: Based on a systematic review of 50 articles, the existing literature indicates that long-term stroke rates and favorable outcomes for surgical revascularization for steno-occlusive disease have improved over time and are lower than previously reported. Improved patient selection, perioperative care, and surgical techniques may contribute to improved outcomes.

Double-Barrel (2-Donor-2-Recipient) Bypass as Rescue Treatment for Patient with Occluded Middle Cerebral Artery Intracranial Stent and Recurrent Ischemia.

Stent occlusion is a challenging complication following endovascular interventions that require intracranial stenting.1-4 Although there are small series describing revascularization for stenoocclusive disease failing best medical management,5-14 there are few reports in the literature regarding surgical bypass as a treatment for stent occlusion.5 We present the case of a 37-year-old man who presented with right-sided weakness, numbness, and difficulty with speech and ambulation. His history is notable for a left M1 (segment of middle cerebral artery) occlusion 6 months prior that was treated with mechanical thrombectomy requiring repeat thrombectomy and rescue acute middle cerebral artery (MCA) stent placement given vessel reocclusion. Diagnostic cerebral angiography demonstrated stent occlusion. Given his continued ischemic symptoms despite best medical management, the patient underwent a double-barrel superficial temporal artery-MCA direct bypass to revascularize the MCA territory. To our knowledge, there is no literature to date describing a 2-donor-2-recipient direct bypass for the rescue treatment of symptomatic intracranial stent occlusion with recurrent ischemia. We review the case presentation, angiographic findings, surgical nuances, and postoperative course with imaging. The patient provided informed consent for the procedure and verbal support for publishing his image and inclusion in this submission.

Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats.

Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500-1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

Effects of testosterone dose on spatial memory among castrated adult male rats.

Previous research on the activational effects of testosterone on spatial memory has produced mixed results, possibly because such effects are dose-dependent. We tested a wide range of testosterone doses using two spatial memory tasks: a working-reference memory version of the radial-arm maze (RAM) and an object location memory task (OLMT). Adult male Sprague-Dawley rats were castrated or sham-castrated and given daily injections of drug vehicle (Oil Sham and Oil GDX) or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.000 mg T) beginning seven days before the first day of behavioral tests and continuing throughout testing. For the RAM, four arms of the maze were consistently baited on each day of testing. Testosterone had a significant effect on working memory on the RAM, with the Oil Sham, 0.125 mg T, and 0.500 mg T groups performing better than the Oil GDX group. In contrast, there was no significant effect of testosterone on spatial reference memory on the RAM. For the OLMT, we tested long-term memory using a 2 h inter-trial interval between first exposure to two identical objects and re-exposure after one object had been moved. Only the 0.125 and 0.500 mg T groups showed a significant increase in exploration of the moved object during the testing trials, indicating better memory than all other groups. Testosterone replacement restored spatial memory among castrated male rats on both behavioral tasks, but there was a complex dose-response relationship; therefore, the therapeutic value of testosterone is likely sensitive to dose.